Post-exposure Prophylaxis Research Articles

Rabies post-exposure prophylaxis: a retrospective analysis of timing of initiation and antibody responses in a Belgian cohort.

BackgroundWe aimed to determine the timeliness of rabies post-exposure prophylaxis (PEP) and the proportion of individuals with an adequate antibody response post-PEP among those attending the Belgian national reference center. MethodsRetrospective analysis of patient records who attended our center from 2018-2023. Delay was defined as rabies immunoglobulin (RIG) and vaccine initiation beyond 2 calendar days after exposure. Antibodies were measured by rapid fluorescent focus inhibition test (RFFIT) after PEP in high-risk exposures. A titer ≥0.5 IU/ml was considered adequate. ResultsWe reviewed 317 patient records. Among individuals with inland exposure (n=103), 85% timely received PEP. Among travelers exposed abroad (n=214), administration of RIG and vaccine initiation were timely in 30% and 50% of cases, respectively. An adequate antibody response was detected in 99.5% (195/196) individuals. ConclusionSubstantial PEP delays among travelers were observed. The robust antibody responses suggest that routine serological follow-up is not necessary for all patients.

Rabies surveillance in the United States during 2022.

To provide comprehensive epidemiological information about the distribution and occurrence of rabies during 2022 in the US, Canada, and Mexico. The US National Rabies Surveillance System collected 2022 animal rabies data from US state and territorial public health departments and USDA Wildlife Services. Temporal and geographic analyses were conducted to evaluate trends in animal rabies cases. During 2022, 54 US jurisdictions reported 3,579 animal rabies cases, reflecting a 2.3% decline from 3,663 cases reported in 2021. Six states collectively reported > 50% of animal rabies cases: Texas (395 [11.0%]), Virginia (337 [9.4%]), Pennsylvania (329 [9.2%]), New York (267 [7.5%]), North Carolina (264 [7.4%]), and California (241 [6.7%]). Out of the total reported rabies animal cases, 3,234 (90.4%) were attributed to wildlife, with bats (1,218 [34.0%]), raccoons (1,014 [28.3%]), skunks (660 [18.4%]), and foxes (269 [7.5%]) representing the primary hosts confirmed with rabies. Rabid cats (222 [6.2%]), cattle (42 [1.2%]), and dogs (50 [1.4%]) constituted > 90% of reported domestic animal rabies cases. In 2022, there was an increase in the number of animal samples submitted for rabies testing in the US and Canada. A notable geographic expansion of gray fox rabies virus variant was detected in the US. Three human rabies deaths due to vampire bat rabies infection occurred in Mexico; none were reported from the US and Canada. Laboratory diagnosis of rabies in animals is critical to ensure judicious use of human rabies postexposure prophylaxis.

Scoping Review of Pre-Exposure Prophylaxis and Post-Exposure Prophylaxis in HIV Prevention in Türkiye

Abstract Background Pre-Exposure Prophylaxis (PrEP) is a medical -antiretroviral- prevention method that reduces the risk of HIV transmission during sexual intercourse or injection drug use. Post-exposure prophylaxis (PEP) refers to taking medicine after risky exposure. The European Centre for Disease Prevention and Control (ECDC) has recommended the integration of PrEP into the existing HIV prevention packages since 2015. In Türkiye, first PrEP Guideline was published in 2022. The aim of this study is to evaluate the literature gap on the PrEP and PEP for HIV prevention research in Türkiye. Methods This study was conducted in October 2023. Searches were performed using the keywords ‘HIV, AIDS’ and ‘Pre-exposure prophylaxis, PrEP, Post-exposure prophylaxis, PEP’ in PubMed, Web of Science, Scopus, TRDizin, and Dergipark for all years. ‘Türkiye, Turkey, Turkish’ were added into the keywords in international indexes, without using country filters. Inclusion criteria were research on PrEP or PEP for HIV, research conducted in or using data from Türkiye, publications in English/Turkish. Exclusion criteria were non-HIV topics, non-Turkish data, non-English/Turkish publications. Lists were merged, duplicates were removed. Inclusion-exclusion criteria were conducted at title and abstract level. Full texts of the included articles examined for bibliometric characteristics, study types, and key results. Results 1014 publications yielded, 993 evaluated, and 17 fully reviewed. Four discussed Türkiye’s PrEP practices (2018-2023); three analyzed PEP regimens; three were reviews on PrEP/PEP in Türkiye (2016-2022). Two original research articles explored PrEP awareness among Türkiye’s men having sex with men (2022) and infectious disease physicians’ attitudes toward PrEP (2020). Studies showed gaps in PrEP information and service access. Conclusions There are limited studies published on PrEP and PEP in HIV prevention in Türkiye. This study highlights the need for local research on the topic. Key messages • Evaluation of Pre-Exposure Prophylaxis (PrEP) and Post-Exposure Prophylaxis (PEP) publications highlights gaps in HIV prevention research. • Limited literature on PrEP and PEP in HIV prevention emphasizing the need for further studies and improved access to PrEP information.

Combined HIV prevention: knowledge and attitudes among higher education students in Portugal

Abstract Introduction Combined Prevention is a strategy that combines different methods of HIV prevention that can be used simultaneously or sequentially, depending on the characteristics and life stage of everyone. Among the methods are condom use, regular HIV testing, pre-exposure prophylaxis (PrEP), and post-exposure prophylaxis (PEP). Combined prevention is particularly important for more vulnerable groups, such as adolescents and young adults. Objectives To investigate the knowledge and attitudes related to combined HIV prevention among college students. Methods A cross-sectional study was conducted with college students from two institutions in a Portuguese city in the year 2022. Sampling was non-probabilistic, by convenience. Students aged 18 to 29 who had initiated sexual activity were included. The data collection instrument was a structured questionnaire sent to students online. Data were analyzed descriptively. Ethical aspects were respected. Results A total of 424 students participated in the study; majority were female (79.2%), white (92.9%), single (96.7%), Catholic (67.2%), with a mean age of 20.8 years (SD = 2.3). The number of sexual partners in the last semester ranged from none to 19, with an average of two partners (SD = 1.9). Nearly all students (94.3%) agreed that condoms are the main form of HIV prevention, however, 45.2% did not use condoms in their last casual sexual encounter. Only 15.5% and 13.9% of participants reported knowing about pre- and post-exposure prophylaxis, respectively. The majority had never been tested for HIV (81.8%) and did not know where tests could be done for free (70.9%). Conclusions Despite higher education, students are vulnerable to HIV and have unsatisfactory knowledge about combined prevention measures. Key messages • College students are young individuals with high vulnerability to contracting HIV and other sexually transmitted infections. • Universities should assume their role as promoters of health and develop strategies that contribute to students’ knowledge and reflection on HIV and its prevention methods.

Molecular characterisation of human rabies in Tanzania and Kenya: a case series report and phylogenetic investigation

BackgroundRabies remains a major public health problem in low- and middle-income countries. However, human rabies deaths are rarely laboratory-confirmed or sequenced, especially in Africa. Five human rabies deaths from Tanzania and Kenya were investigated and the causative rabies viruses sequenced, with the aim of identifying implications for rabies control at individual, healthcare and societal levels.Case presentationThe epidemiological context and care of these cases was contrasting. Four had a clear history of being bitten by dogs, while one had an unclear biting history. Two individuals sought medical attention within a day of being bitten, whereas three sought care only after developing rabies symptoms. Despite seeking medical care, none of the cases received complete post-exposure prophylaxis: one patient received only tetanus vaccination, one did not complete the post-exposure vaccination regimen, one followed an off-label vaccination schedule, and two did not receive any post-exposure vaccinations before the onset of symptoms. These cases highlight serious gaps in health-seeking behaviour, and in health systems providing appropriate care following risky exposures, including in the accessibility and effectiveness of post-exposure prophylaxis as it is administered in the region.ConclusionsThe viral genomic and epidemiological data confirms dog-mediated rabies as the cause of each of these deaths. The phylogenetic investigation highlights the transboundary circulation of rabies within domestic dog populations, revealing distinct rabies virus clades with evidence of regional spread. These findings underscore the importance of coordinated cross-border control efforts between the two countries. Urgent action is needed to improve awareness around the need for emergency post-exposure vaccines that should be accessible in local communities and administered appropriately, as well as investment in coordinated dog vaccination to control dog-mediated rabies, the underlying cause of these deaths.Graphical

Closing the Gaps: Testing the Efficacy of Carbapenem and Cephalosporin Treatments of Late-Stage Anthrax in Rabbits

Anthrax is a fatal zoonotic disease caused by exposure to Bacillus anthracis spores. The CDC’s guidelines divide anthrax treatment into three categories according to disease progression: post-exposure prophylaxis (PEP), systemic, and systemic with a suspicion of CNS infection. While the prognosis for PEP or the early treatment of systemic anthrax is very good, ingress of the bacteria into the CNS poses a substantial clinical challenge. Here, we use rabbits to test the efficacy of a combined treatment of meropenem and doxycycline, which is the first choice in the CDC recommendations for treating systemic patients with an indication of CNS infection. In addition, we test the efficacy of the first-generation cephalosporin, cefazolin, in treating different stages of the disease. We found that the combination of doxycycline and meropenem is highly effective in treating rabbits in our inhalation model. Cefazolin was efficient only for PEP or systemic-stage treatment and not for CNS-infected animals. Our findings support the CDC recommendation of using a combination of doxycycline and meropenem for systemic patients with or without indications of CNS infection. We found that cefazolin is a decent choice for PEP or early-stage systemic disease but recommend considering using this antibiotic only if all other options are not available.

Rabies epidemiology in the central of Tunisia: A Call for a One-Health Approach

Abstract Background Advocating for a One-Health approach is crucial for ensuring effective rabies surveillance in Africa, including Tunisia. Collecting information is essential to evaluate the prevalence of dog bites and rabies in Tunisia. To address this, we conducted an analysis of reported incidents in the central region of Tunisia from 2019 to 2022. This analysis aimed to generate valuable insights that can inform strategies for rabies elimination in Tunisia, highlighting the importance of the One-Health approach. Methods We carried out a descriptive study using surveillance data from Monastir governorate in Central Tunisia. All humans exposed to animals, residents in Monastir Governorate and declared to the regional directorate of primary health care from January 1, 2019 to December 31, 2022 were included in our study. Data were entered, cleaned, and analyzed using Excel. Results During the studied period, 7789 cases of human exposures to animals were reported with an annual average of 1969 ± 207 exposures per year. The annual incidence rate of exposure to animal bites was 324 per 100,000 population. The sex-ratio was 2.07 and almost one third of exposed humans were aged less than 15 years-old. The most listed offending animals were dogs (65.2%), followed by cats (24.4%). The number of exposures by unvaccinated dogs increased significantly during our study period. Post-exposure prophylaxis (PEP) was applied among 99% (n = 7772) of declared exposures. Among them, 2.5% (n = 202) did not complete the PEP recommended protocol. During our study period, rabies was confirmed in 39 animals. Two fatal human rabies cases were declared respectively in 2021 and 2022. Conclusions Rabies remains a worrying health problem in Tunisia with a high percentage reported among youth and males. Targeting children and adolescents by education and information campaigns about preventive measures and mass dog vaccination are the key to ending this scourge. Key messages • It is crucial to reinforce preventive strategies, such as mass dog vaccination programs. • Public awareness about rabies prevention should be enforced in order to decrease Human rabies risks.

Knowledge, Attitude and Practice of Nurses and Midwives towards Hepatitis B Infection and Control Measures in Alban Gaded Hospital, Khartoum, Sudan

Purpose: Infection with the hepatitis B virus (HBV) causes severe morbidity and death, burdening world health. Nurses and midwives, among other healthcare professionals, are more likely to contract the illness. Few studies have looked at the knowledge, attitude, and practices (KAP) of healthcare professionals in Sudan with regard to HBV infection, despite the fact that diverse components of KAP have an impact on health-related behaviors. This study's objective was to assess the knowledge, attitude, and practice (KAP) level of nurses and midwives concerning HBV viral infection in, Khartoum, Sudan.  Methods: In the Sudanese state of Khartoum, a public hospital (Alban Gaded Hospital) underwent a cross-sectional descriptive hospital-based study. To assess KAP's understanding of nurses and midwives about HBV infection. Self-administered questionnaires were used and approved by the supervisor for distribution to the population chosen for the study. The data was handed over to the Medical Director whom personally ensured the questionnaires were signed and filled by the Healthcare workers (HCWs) of the chosen criteria at the field. A member of group (23:B) took care of the supervision aside with the medical director, and made sure the data was collected as needed. The data at hand were subjected to statistical analysis using SPSS version 24.0 (Statistical Package for Social Sciences).  Results: 95 samples out of 99 were collected. According to participants’ knowledge: 67.95% have good knowledge about HBV, while 32.05% lack basic knowledge about it. The participants’ attitude towards HBV is above average showing 60.3% safe attitude. Lastly, the study shows excellent practice of the participants’ behavior towards HBV safety measures with a score of 92.3% safe practice. From the hospital, a total of 95 out of 99 nurses and midwives took part in the study. Two thirds of the respondents practiced safety, and the majority of respondents had a positive attitude about HBV preventative measures. More than half of the respondents (58.2%) had an average level of understanding. A minor but serious score of (12.6%) was noticed of the individuals, dealing with patients without wearing gloves. More over half of the nurses and midwives were not vaccinated against HBV; more than 50% of participants had incorrect ideas regarding the symptoms and route of HBV infection and all 95 participants voted (NO) for ever being infected by HBV.  Conclusion: In Alban Gaded hospital, the majority of the nurses and midwives were aware of HBV infection. But a sizeable majority of the participants lacked the necessary understanding of early immunization after birth. The study found a probability of high risk infection due to exposure under the poor level of HBV vaccine coverage rate. Moreover a clear point of limitation was noticed in Table 4 third question, where it asks whether you are or ever was infected by HBV. All the participants denied, showing a sense of partiality. Further occupational exposure prevention measures, training programs on HBV infection, including post-exposure prophylaxis, and increasing the vaccination rate of all HCWS are also strongly encouraged.

Generalized tetanus complicated with Takotsubo-cardiomyopathy in a septuagenarian following a laceration injury with soil contamination – a case report

BackgroundTetanus is a clinical rarity due to the successful globally adopted childhood vaccination programme. The rising elderly population in the United Kingdom creates a subset of individuals whom are prone to develop Tetanus as they preceded this vaccination drive.Case summaryA 76 year old Caucasian lady presented with a soil contaminated laceration injury on her knee following a fall. Though she received urgent assessment and wound care, the relevance of the injury in the backdrop of her age was not appreciated and her tetanus post exposure prophylaxis was overlooked. She readmitted seeking further management 1 week later with an infected wound with Trismus and clinical features favoring Generalized tetanus. During her stay she developed Takotsubo-cardiomyopathy with congestive cardiac failure and required prolonged care in the intensive unit with mechanical ventilation and rehabilitation before being discharged home.ConclusionFirst contact physicians should have a greater appreciation of the types of injuries and at-risk individuals who are more prone to develop tetanus upon exposure to ensure early and appropriate identification. There should be greater situational awareness with regard to the elderly in view of their heightened risk of development of tetanus specially those born before the vaccination drive. Knowledge regarding post exposure prophylaxis measures for tetanus should be regularly updated using local guidance to ensure awareness, so as to despite its rarity Tetanus remains an adequately appreciated disease.

Safety of single-dose bedaquiline combined with rifampicin for leprosy post-exposure prophylaxis: A Phase 2 randomized non-inferiority trial in the Comoros Islands.

To reduce leprosy risk in contacts of patients with leprosy by around 50%, the World Health Organization (WHO) recommends leprosy post-exposure prophylaxis (PEP) using single-dose rifampicin (SDR). Results from a cluster randomized trial in the Comoros and Madagascar suggest that PEP with a double dose of rifampicin led to a similar reduction in incident leprosy, prompting the need for stronger PEP. The objective of this Phase 2 trial was to assess safety of a bedaquiline-enhanced PEP regimen (intervention arm, bedaquiline 800 mg with rifampicin 600 mg, BE-PEP), relative to the WHO recommended PEP with rifampicin 600 mg alone (control arm, SDR-PEP). From July 2022 to January 2023, consenting participants were screened for eligibility, including a heart rate-corrected QT interval (QTc) <450 ms and liver enzyme tests (ALT/AST) below 3× the upper limit of normal (ULN), before they were individually randomized 1:1 in an open-label design. Recruitment was sequential, by age group. Pediatric dosages were weight adjusted. Follow-up was done at day 1 post-dose (including ECG) and day 14 (including ALT/AST), with repeat of ALT/AST on the last follow-up at day 30 in case of elevation on day 14. The primary outcome was non-inferiority of BE-PEP based on a <10 ms difference in QTc 24 h after treatment administration, both unadjusted and adjusted for baseline QTc. Of 408 screened participants, 313 were enrolled, starting with 187 adults, then 38 children aged 13 to 17 years, and finally 88 children aged 5 to 12 years, of whom 310 (99%) completed all visits. Across all ages, the mean QTc change on BE-PEP was from 393 ms to 396 ms, not significantly different from the change from 392 ms to 394 ms on SDR-PEP (difference between arms 1.8 ms, 95% CI -1.8, 5.3, p = 0.41). No individual's QTc increased by >50 ms or exceeded 450 ms after PEP administration. Per protocol, all children were analyzed together, with no significant difference in mean QTc increase for BE-PEP compared to SDR-PEP, although non-inferiority of BE-PEP in children was not demonstrated in unadjusted analysis, as the upper limit of the 95% CI of 10.4 ms exceeded the predefined margin of 10 ms. Adjusting for baseline QTc, the regression coefficient and 95% CI (3.3; -1.4, 8.0) met the 10 ms non-inferiority margin. No significant differences in ALT or AST levels were noted between the intervention and control arms, although a limitation of the study was false elevation of ALT/AST during adult recruitment due to a technical error. In both study arms, one serious adverse event was reported, both considered unlikely related to the study drugs. Dizziness, nausea, headache, and diarrhea among adults, and headaches in children, were nonsignificantly more frequently observed in the BE-PEP group. In this study, we observed that safety of single-dose bedaquiline 800 mg in combination with rifampicin is comparable to rifampicin alone, although non-inferiority of QTc changes was demonstrated in children only after adjusting for the baseline QTc measurements. A Phase 3 cluster randomized efficacy trial is currently ongoing in the Comoros. ClinicalTrials.gov NCT05406479.

Safety Evaluation of the Novel Cocktail of Monoclonal Antibodies for Postexposure Prophylaxis in Category III Animal Exposures

Abstract Introduction: Rabies monoclonal antibody (mAb) is a life-saving immune-biological for postexposure prophylaxis (PEP) in all Category III animal exposures. A novel cocktail of mAbs derived using recombinant DNA technology is presently available for usage. The WHO recommends monitoring the clinical use and outcomes of mAb products. Methods: An open-label, postmarketing study was conducted at the anti-rabies clinic in the southern part of India. PEP was provided to all the study participants per the national guidelines. All the subjects were assessed for any adverse events (AEs) following PEP up to 35 days; if any, were treated free of cost at the study center. Results: The present study included 309 subjects across all age groups, 59.2% were adults, 33.3% of children, and 7.5% elderly. Majority of the patients were exposed to dogs (89.6%) and most of them had lacerations (86.3%) in different parts of their body. A total of 19 (6.2%) AEs were reported. All the AEs were local reactions, namely pain (2.6%), erythema (1.4%), tenderness (1%), induration (0.6%), and swelling (0.6%). All reported AEs were mild (Grade 1 severity) and resolved completely with symptomatic treatment. Conclusion: The novel cocktail of mAbs was safe for PEP in Category III animal exposures across all the age groups and supports its continued and improved usage for Universal Health Coverage to prevent rabies.

Notes from the Field: Enhanced Surveillance for Raccoon Rabies Virus Variant and Vaccination of Wildlife for Management - Omaha, Nebraska, October 2023-July 2024.

On September 28, 2023, a kitten aged approximately 6 weeks found in Omaha, Nebraska, had test results positive for rabies at the Nebraska Veterinary Diagnostic Center (NVDC) after dying with neurologic signs and having bitten and scratched its caretakers. Preliminary investigation identified 10 exposed persons for whom postexposure prophylaxis (PEP)† was recommended. Subsequent variant-typing by NVDC yielded a presumptive positive result for the Eastern raccoon rabies virus variant (RRVV), which CDC confirmed on October 6.

Incomplete Immunity for Varicella and Measles in Pediatric Organ Transplant Candidates. Real World Experience From an Infectious Diseases Pre-Transplantation Clinic.

Vaccinating pediatric solid organ transplant candidates against measles and varicella is crucial due to the risk of severe disease in immunosuppressed recipients and general avoidance of live virus vaccines post-transplantation. The world saw a resurgence of measles starting 2012 prompting the American Society of Transplantation in 2015 to release guidelines on recognition, prevention, and post-exposure prophylaxis of this disease in solid transplant recipients. This study aims to assess the extent of incomplete immunity to these viruses in candidates and the approach to immunity optimization during a period of heightened awareness. A cross-sectional study from 2012 to 2016 at Cleveland Clinic Children's included pediatric solid organ transplant candidates. Data on vaccination history, serology, and demographics were collected. Incomplete immunity was defined by incomplete vaccination or seronegativity. Among 91 candidates, 54.9% had complete varicella vaccination. Serological varicella immunity among patients tested varied by age: < 7 years, 50.0% positive in patients with complete schedules, none in the incomplete; ≥ 7 years, 50.0% positive in patients with complete schedules, 65.5% in the incomplete. For measles, 69.2% had complete vaccination, with immunity varying by age among those tested: < 7 years, 84.6% positive in patients with complete schedules, 42.9% in the incomplete; ≥ 7 years, 81.0% with complete, 62.5% with incomplete. Only 31.1% of those who qualified for a varicella additional dose and 28% who qualified for an additional measles dose received it, respectively. Incomplete immunity to varicella and measles was prevalent in pediatric solid organ transplant candidates at our center during the study period. Despite an increase in global measles activity, our efforts to optimize immunity through additional vaccine doses were only partially successful. Future research should focus on addressing strategies and understanding barriers to ensure timely vaccination for this vulnerable population prior to transplant, especially during periods of increased viral activity.

Impact of doxycycline post-exposure prophylaxis for sexually transmitted infections on the gut microbiome and antimicrobial resistome.

Doxycycline post-exposure prophylaxis (doxy-PEP) reduces bacterial sexually transmitted infections among men who have sex with men and transgender women. Although poised for widespread clinical implementation, the impact of doxy-PEP on antimicrobial resistance remains a primary concern as its effects on the gut microbiome and resistome, or the antimicrobial resistance genes (ARGs) present in the gut microbiome, are unknown. To investigate these effects, we studied participants from the DoxyPEP trial, a randomized clinical trial comparing doxy-PEP use, a one-time doxycycline 200-mg dose taken after condomless sex (DP arm, n = 100), to standard of care (SOC arm, n = 50) among men who have sex with men and transgender women. From self-collected rectal swabs at enrollment (day-0) and after 6 months (month-6), we performed metagenomic DNA sequencing (DNA-seq) or metatranscriptomic RNA sequencing (RNA-seq). DNA-seq data were analyzable from 127 samples derived from 89 participants, and RNA-seq data were analyzable from 86 samples derived from 70 participants. We compared the bacterial microbiome and resistome between the two study arms and over time. The median number of doxycycline doses taken since enrollment by participants with DNA-seq data was zero (interquartile range (IQR): 0-7 doses) for the SOC arm and 42 (IQR: 27-64 doses) for the DP arm. Tetracycline ARGs were detected in all day-0 DNA-seq samples and in 85% of day-0 RNA-seq samples. The proportional mass of tetracycline ARGs in the resistome increased between day-0 and month-6 in DP participants from 46% to 51% in the metagenome (P = 2.3 × 10-2) and from 4% to 15% in the metatranscriptome (P = 4.5 × 10-6), but no statistically significant increases in other ARG classes were observed. Exposure to a higher number of doxycycline doses correlated with proportional enrichment of tetracycline ARGs in the metagenome (Spearman's ρ = 0.23, P = 9.0 × 10-3) and metatranscriptome (Spearman's ρ = 0.55, P = 3.7 × 10-8). Bacterial microbiome alpha diversity, beta diversity and total bacterial mass did not differ between day-0 and month-6 samples from DP participants when assessed by either DNA-seq or RNA-seq. In an abundance-based correlation analysis, we observed an increase over time in the strength of the correlation between tetracycline ARGs and specific bacterial taxa, including some common human pathogens. In sum, doxy-PEP use over a 6-month period was associated with an increase in the proportion of tetracycline ARGs comprising the gut resistome and an increase in the expression of tetracycline ARGs. At 6 months of doxy-PEP use, no residual differences were observed in alpha and beta diversity or taxonomic composition of the gut microbiome. As doxy-PEP is implemented as a public health strategy, further studies and population-level surveillance of doxycycline-resistant pathogens are needed to understand the implications of these findings. ClinicalTrials.gov registration number: NCT03980223 .

Safety assessment of the world’s first novel cocktail of two monoclonal antibodies in WHO category-III animal-bite patients

ABSTRACT Background: Rabies, a zoonotic disease, poses a significant global public health challenge, and post-exposure prophylaxis (PEP) is crucial for prevention. Monoclonal antibodies (mAbs) have emerged as a promising alternative to rabies immunoglobulins due to their high efficacy and standardized manufacturing process. Materials and Methods: A prospective, open-label post-marketing surveillance study was conducted with patients of WHO category-III suspected rabid animal bites. TwinRab™, a novel cocktail of docaravimab and miromavimab, was administered at a dosage of 40 IU/kg in and around the wound, along with the anti-rabies vaccine, which was administered intradermal as per Thai Red Cross regimen. Results: In this study, 200 subjects received TwinRab™ with a 100% completion rate. Three (1.5%) patients showed solicited local AEs, and two (1%) patients showed solicited systemic AEs, which were resolved after appropriate treatment intervention. The overall tolerability assessment showed positive ratings from doctors (94%) and patients (74%). Conclusion: The post-marketing surveillance study demonstrated the safety of TwinRab™ in patients who experienced category-III suspected rabid animal bites, thereby supporting its potential as an alternative option for PEP in the management of animal bite for the prevention of rabies.

Effects of doxycycline post-exposure prophylaxis for prevention of sexually transmitted infections on gonorrhoea prevalence and antimicrobial resistance among men who have sex with men in the USA: a modelling study

Doxycycline post-exposure prophylaxis (PEP) has been shown to be efficacious for the prevention of bacterial sexually transmitted infections, but resistance implications for Neisseria gonorrhoeae remain unknown. We aimed to use a mathematical model to investigate the anticipated impact of doxycycline PEP on the burden of gonorrhoea and antimicrobial resistance dynamics in men who have sex with men (MSM) in the USA. Using a deterministic compartmental model, characterising gonorrhoea transmission in a US MSM population comprising three sexual activity groups defined by annual partner turnover rates, we introduced doxycycline PEP at various uptake levels (10-90%) among those with high sexual activity. Infections were stratified by symptom status and resistance profile (ie, susceptible, ceftriaxone-resistant, tetracycline-resistant, or dual-resistant), with ceftriaxone the treatment for active infection. As resistance to tetracycline, not doxycycline, is monitored and reported nationally, we used this as a proxy for doxycycline PEP resistance. We compared the 20-year prevalence, incidence rates, and cumulative incidence of gonococcal infection, resistance dynamics (time to 5% prevalence of ceftriaxone resistance, 5% prevalence of dual resistance, and 84% prevalence of tetracycline resistance), and antibiotic consumption with baseline (ie, no doxycycline PEP). Uptake of doxycycline PEP resulted in substantial reductions in the prevalence and incidence of gonorrhoea, but accelerated the spread of tetracycline resistance. The maximum reduction in prevalence over 20years compared with no uptake ranged from 40·3% (IQR 15·3-83·4) with 10% doxycycline PEP uptake to 77·4% (68·4-84·9) with 90%uptake. Similarly, the maximum reduction in the incidence rate ranged from 38·6% (14·1-83·6) with 10% uptake to 77·6% (68·1-84·7) with 90% uptake. Cumulative gonococcal infections were reduced by a median of 14·5% (IQR8·4-21·6) with 10% uptake and up to 46·2% (26·5-59·9) with 90% uptake after 5years, and by 6·5% (3·4-13·0) with 10% uptake and 8·7% (4·3-36·2) with 90% uptake by 20years. In almost all scenarios explored, doxycycline PEP lost clinical effectiveness (defined as 84% prevalence of tetracycline resistance) within the 20-year period, but itslifespan ranged from a median of 12·1years (IQR 9·9-15·7) with 10% uptake to 1·6years (1·3-1·9) with 90%uptake. Doxycycline PEP implementation had minimal impact on extending the clinical lifespan of ceftriaxone monotherapy (5·0years [IQR 4·0-6·2]), with the median time to 5% prevalence of resistance ranging from 4·8years (3·9-6·0) for 90% uptake to 5·0years (4·1-6·2) for 10% uptake. Similarly, the median time to 5%prevalence of dual resistance to ceftriaxone and tetracycline ranged from 4·8years (3·9-6·0) for 90% uptake to 5·8years (4·8-7·4) for 10% uptake. Median decrease in ceftriaxone consumption for high doxycycline PEP uptake levels compared with baseline ranged from 41·7% (27·0-54·3) for 50% uptake to 50·2% (29·3-62·7) for 90% uptake at 5years, but dropped to 11·8% (6·9-32·0) for 50% uptake and 12·1% (7·0-41·6) for 90% uptake after 20years. Notwithstanding the clear benefits of doxycycline PEP for other sexually transmitted infections, for Ngonorrhoeae, model findings suggest that doxycycline PEP is an effective but impermanent solution for reducing infection burden, given eventual selection for resistant strains. This finding presents a challenge for policy makers considering strategies for doxycycline PEP implementation and oversight: the need to balance the clear, short-term clinical benefits with the risk of harm via antimicrobial resistance. US Centers for Disease Control and Prevention, National Institute of Allergy and Infectious Diseases.

Dynamic choice HIV prevention with cabotegravir long-acting injectable in rural Uganda and Kenya: a randomised trial extension

HIV infections are ongoing globally despite efficacious biomedical prevention options. We sought to determine whether an HIV prevention package providing choice of daily pills or long-acting injectable cabotegravir and opportunities to change prevention options could increase biomedical prevention coverage and reduce new HIV infections. This study was an extension of three randomised trials that used SEARCH dynamic choice HIV prevention to recruit adults (aged ≥15 years) at risk for HIV from antenatal, outpatient, and community settings in rural Uganda and Kenya. In this 48-week open-label extension, participants maintained their original (1:1) randomisation group; the option to choose cabotegravir long-acting injectable was added for intervention participants. Inclusion criteria for the extension were previous enrolment in a SEARCH dynamic choice HIV prevention trial, negative HIV rapid test, and residence in study region. The intervention provided person-centred choice of oral pre-exposure prophylaxis (PrEP) or post-exposure HIV prophylaxis (PEP) or cabotegravir long-acting injectable, with the option to switch according to participant preference. The control provided standard-of-care access to oral PrEP and PEP, but not cabotegravir long-acting injectable. Biomedical prevention coverage (proportion of follow-up covered by oral PrEP, PEP, or cabotegravir long-acting injectable; primary outcome) and HIV incidence (secondary outcome) were compared between groups using targeted minimum loss-based estimation. The trial (NCT05549726) is closed to recruitment. Of 1534 participants initially randomly assigned (from April 15, 2021 to Sept 29, 2022), 984 (487 in the intervention group and 497 in the standard-of-care group) reconsented to the extension (from Jan 2 to March 3, 2023). The mean proportion of follow-up covered by biomedical HIV prevention was 69·7% (95% CI 64·9-74·5) in the intervention group versus 13·3% (10·2-16·3) in the standard-of-care group, corresponding to an absolute difference of 56·4 percentage points (95% CI 50·8-62·1; p<0·0001). The intervention significantly improved coverage across prespecified subgroups (sex and age groups). During the study, 274 (56%) of 485 intervention participants used cabotegravir long-acting injectable, 255 (53%) used oral PrEP, and ten (2%) used PEP. Among cabotegravir long-acting injectable initiators, 118 (43%) of 274 were not previously using oral PrEP or PEP. There were seven incident HIV infections in 390 person-years of follow-up in the standard-of-care group and no infections in 400 person-years of follow-up in the intervention group (incidence rate difference per 100 person-years 1·8, 95% CI 0·4-3·2; p=0·014). Offering people the choice of HIV biomedical prevention options including cabotegravir long-acting injectable in a flexible model can increase prevention coverage and reduce incident HIV infections. HIV programmes should support dynamic choice HIV prevention programmes that include effective oral and injectable long-acting products. National Institutes of Health.

Surgical Management of Pediatric Dog Bites: A Systematic Review and Treatment Guideline

IntroductionDog bites are a unique and unusual injury in children, associated with atypical bacterial species, high infection rates, and controversial surgical treatment. Expert recommendations currently guide management and no surgical evidence-based guidelines exist. We conducted a systematic review to answer three management questions: (1) What are the best practices for wound management? (2) In what circumstances should prophylactic antibiotics be administered? (3) In what circumstances should rabies prophylaxis be given? MethodsA structured review was performed using a keyword search querying “pediatric” “dog bite” “management”. Results were reported according to the PRISMA methodology. The quality of nonrandomized studies was evaluated according to Methodological Index for Non-Randomized Studies (MINORS). Qualitative analysis was performed. ResultsA total of 803 studies were identified and 53 studies were included in the final analysis. Current literature suggests that primary closure of bites which are well irrigated and sharply debrided within 8 h of injury, is not associated with increased infection. While dog bites are associated with an overall high rate of infection (6–25 %), routine antibiotic prophylaxis in low-risk wounds does not lower that risk. Postexposure prophylaxis for rabies is indicated for all dog bites where the rabies status of the dog cannot be determined, or the animal cannot be quarantined for 10 days. ConclusionHigh-quality evidence regarding the surgical management of pediatric dog bites is limited. Trial data have demonstrated improved outcomes in wound healing and infection rates with a focus on copious irrigation and diligent wound debridement, although independent validation is needed. Level of EvidenceLevel II – systematic review.

Syphilis testing, incidence, and reinfection among gay and bisexual men in Australia over a decade spanning HIV PrEP implementation: an analysis of surveillance data from 2012 to 2022

Gay and bisexual men (GBM) remain overrepresented among syphilis diagnoses in Australia and globally. The extent to which changes in sexual networks associated with HIV pre-exposure prophylaxis (PrEP) and treatment as prevention (TasP) may have influenced syphilis transmission among GBM at the population-level is poorly understood. We describe trends in syphilis testing and incidence among GBM in Australia over eleven years spanning widespread uptake of HIV PrEP and TasP. We analysed linked clinical data from GBM aged 16 years or older across a sentinel surveillance network in Australia from January 1, 2012, to December 31, 2022. Individuals with at least two clinic visits and with at least two syphilis tests during the observations period were included in testing and incidence analyses, respectively. Annual rates of testing and infectious syphilis incidence from 2012 to 2022 were disaggregated by HIV status and PrEP use (record of PrEP prescription; retrospectively categorised as ever or never-PrEP user). Cox regression explored associations between demographics, PrEP use and history of bacterial sexually transmissible infections (STIs) and infectious syphilis diagnosis. Among 129,278 GBM (mean age, 34.6 years [SD, 12.2]) included in testing rate analyses, 7.4% were living with HIV at entry and 31.1% were prescribed PrEP at least once during the study period. Overall syphilis testing rate was 114.0/100 person-years (py) and highest among GBM with HIV (168.4/100 py). Syphilis testing increased from 72.8/100 py to 151.8/100 py; driven largely by increases among ever-PrEP users. Among 94,710 GBM included in incidence analyses, there were 14,710 syphilis infections diagnosed over 451,560 person-years (incidence rate=3.3/100 py). Syphilis incidence was highest among GBM with HIV (6.5/100 py), followed by ever-PrEP users (3.5/100 py) and never-PrEP users (1.4/100 py). From 2012 to 2022, syphilis incidence increased among ever-PrEP users from 1.3/100 py to 5.1/100 py, and fluctuated between 5.4/100 py and 6.6/100 py among GBM with HIV. In multivariable Cox regression, previous syphilis diagnosis (adjusted hazard ratio [aHR]=1.98, 95% CI=1.83-2.14), living with HIV (aHR=1.83, 95% CI=1.12-1.25) and recent (past 12m) prescription of PrEP (aHR=1.78, 95% CI=1.61-1.97) were associated with syphilis diagnosis. Syphilis trends between GBM with HIV and GBM with evidence of PrEP use have converged over the past decade in Australia. Our findings recommend targeting emergent syphilis control strategies (e.g. doxycycline post-exposure prophylaxis) to GBM with prior syphilis diagnoses, using HIV PrEP or who are living with HIV. Australian Department of Health and Aged Care, National Health and Medical Research Council.

Standardization And Evaluation Of An In-House ELISA For The Detection Of Rabies Antibody In A Tertiary Care Centre In South India

BackgroundRapid fluorescent focus inhibition test (RFFIT), a neutralization-based assay for detecting rabies antibodies, is the gold standard. The National Action Plan for Dog Mediated Rabies Elimination (NAPRE) is a national program that strategizes the establishment of enzyme-linked immunosorbent assays (ELISA) to detect rabies antibodies. ObjectiveWe developed an in-house ELISA to screen for rabies antibodies using rabies vaccine antigen to study vaccine response among health care workers (HCWs) who received pre-exposure prophylaxis and a few animal bite victims who received post-exposure prophylaxis with rabies vaccine. Study designA prospective study was carried out from April to September 2023 at the Department of Clinical Virology of a tertiary care center in South India. A total of 161 serum specimens, which included 155 serum samples from study participants and 6 samples from a reference laboratory (as controls), were obtained during the study period. Rabies antibody was determined by the in-house standardized ELISA developed using the rabies vaccine and compared with the reference assay, RFFIT. The accuracy indices of the in-house ELISA were estimated by MedCalc software (version 22.023). ResultsA panel of 86 positive and 75 negative serum samples was used for evaluating the in-house standardized ELISA. The sensitivity, specificity, positive and negative predictive values of the in-house ELISA were 98.8%, 100%, 100%, and 98.7% respectively. The accuracy of the in-house ELISA is 99.4%. ConclusionELISA can be a practically feasible and less expensive assay compared to RFFIT which is a cumbersome procedure with a long turn-around time of 3-4 days.